Evidence map›Paper›PMID 39939803›Full record

ArticleActa pharmacologica Sinica2025

Acyl-CoA thioesterase 8 induces gemcitabine resistance via regulation of lipid metabolism and antiferroptotic activity in pancreatic ductal adenocarcinoma.

Bo-Rui Li, Ting Wang, Hai-Feng Hu, Di Wu, Chen-Jie Zhou, Shun-Rong Ji, Qi-Feng Zhuo, Zheng Li, Zhi-Liang Wang, Gui-Xiong Fan and 6 more

Abstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Lipid Droplets in Cancer: New Insights and Therapeutic Potential.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Bo-Rui Li *Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Ting Wang *Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Hai-Feng Hu *Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Di Wu *Department of Hepatopancreatobiliary, Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Chen-Jie ZhouDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Shun-Rong JiDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Qi-Feng ZhuoDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Zheng LiDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Zhi-Liang WangDepartment of Hepatopancreatobiliary, Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Gui-Xiong FanDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
De-Sheng JingDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Chong-Yuan YuDepartment of Hepatopancreatobiliary, Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Yi QinDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Xue-Min ChenDepartment of Hepatopancreatobiliary, Third Affiliated Hospital of Soochow University, Changzhou, 213000, China. czcxm007@126.com.
Jun-Feng XuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. xujunfeng@fudanpci.org.
Xiao-Wu XuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. xuxiaowu@fudanpci.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) comprises a group of highly malignant tumors of the pancreas. Metabolic reprogramming in tumors plays a pivotal role in promoting cancer progression. However, little is known about the metabolic alterations in tumors that drive cancer drug resistance in patients with PDAC. Here, we identified acyl-CoA thioesterase 8 (ACOT8) as a key player in driving PDAC gemcitabine (GEM) resistance. The expression of ACOT8 is significantly upregulated in GEM-resistant PDAC tissues and is closely associated with poor survival in patients with PDAC. Gain- and loss-of-function studies have shown that ACOT8 drives PDAC GEM resistance both in vitro and in vivo. Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines. The combination of orlistat, an ACOT8 inhibitor, and GEM significantly inhibited tumor growth in PDAC organoid and mouse models. This study reveals the biological importance of ACOT8 and provides a potential combination therapy for treating patients with advanced GEM-resistant PDAC.

Indexed as

Antimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalDeoxycytidineDrug Resistance, NeoplasmLipid MetabolismPalmitoyl-CoA HydrolasePancreatic NeoplasmsThiolester HydrolasesAnimalsCell Line, TumorFerroptosisGemcitabineHumansMaleMiceMice, NudeAcot8 protein, mouseAntimetabolites, AntineoplasticDeoxycytidineGemcitabineOrlistatPalmitoyl-CoA HydrolaseThiolester Hydrolases

Identifiers

PMID39939803
PMCPMC12098905

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.